The retina is a complex structure that contains photoreceptor cells, a network of nerve cells, blood vessels and a metabolically active retinal pigment epithelium. Common retinal diseases that affect retinal metabolism include age-related macular degeneration, diabetic retinopathy and glaucoma, which may cause visual loss and blindness.
Known retinal imaging technology provides some structural and functional information about retinal function and hence retinal diseases.
Thus a scanning laser ophthalmoscope disclosed in R. H. Webb, G. W. Hughes, and O. Pomerantzeff, Flying spot TV ophthalmoscope, Applied Optics 19, 2991-2997, 1980, uses a laser scanning light source to image a retina, subsequently combined with a confocal optical filter to select some light reflected from the retina.
Scanning laser ophthalmoscope indirect mode imaging, for analysing indirectly-reflected light, which uses an annular aperture and stop to block on-axis reflections to form an image from laterally scattered light reflections, is disclosed in Ann E Elser, Stephen A. Burns, John J Weitter, Francois C Delori, Infrared imaging of sub-retinal structures in the human ocular fundus, Vision Res. Vol. 36, No 1, pp. 191-205, 1996.
Retinal oximetry produces a numerical value measurement of the percentage oxygen saturation of blood in retinal arteries and veins. A small region of multi-spectral retinal images of a retinal blood vessel and small adjacent region of the retina is selected for analysis and a numerical percentage oxygen saturation of blood in the blood vessel calculated.
The retinal metabolic image changes over the duration of a heartbeat. With the arrival of a retinal arterial pulse there is an increase of retinal haemoglobin oxygenation. This is followed by a fall in retinal haemoglobin oxygenation, due to oxygen consumption within the metabolically active retinal tissue, before the next retinal arterial pulse.
U.S. Pat. No. 6,244,712 discloses optical scanning spectroscopic retinal blood vessel oximetry using a plurality of wavelengths to illuminate successive portions of the retina and form an interlaced retinal data frame, to avoid over-illuminating an eye by scanning with the plurality of wavelengths simultaneously. The interlaced retinal data frame may be de-interlaced to form plural monochromatic retinal images corresponding to the respective wavelengths. Signals from the eye may be filtered or selected with confocal or anti-confocal filters before being delivered to a detector. The laser scans may be triggered, for example in response to an r-wave of an electrocardiogram, at a predetermined point in a cardiac cycle thereby permitting a detailed analysis of one or more phases of the cardiac cycle.
US 2002/0188203 discloses measurement of blood oxygen saturation in a retinal blood vessel by detecting light that has made a single pass through the retinal blood vessel, i.e. retinal vein or artery, and then been diffused laterally through retinal and/or choroidal layers and left the eye without again passing through the retinal blood vessel. An anti-confocal optical filter, with an aperture and central stop, is used to isolate such single-pass optical signals and thereby simplify calculation of retinal blood oxygen saturation, resulting in increased accuracy of measurement of oxygen saturation. This provides an objective assessment of retinal haemoglobin oxygenation within a small portion of the retinal blood vessel. It is suggested that such measurements can be used to monitor cardiac output of a subject or detect and determine a rate of blood loss.
A retinal metabolic image changes in response to a light stimulus of the retina caused by an increase in retinal neuronal metabolic activity and therefore of oxygen consumption.
US 2004/0075812 discloses detection of changes in reflectance of near-infrared light from the retina of human subjects, caused by changes in oxygen saturation in response to visual activation of the retina by a light pattern or other light stimulus. This provides an objective assessment of inner retinal function, allowing detection, at an early stage, of a regional defect caused by glaucoma.
Haemoglobin oxygenation saturation light absorption is disclosed by, Van Assendelft OW. Spectrophotometry of haemoglobin derivatives. Royal Vangorcum, Assen, The Netherlands: Thomas, 1970.
WO 02/080759 discloses a retinal function camera in which use of isoreflective points enables isolation of retinal haemoglobin oxygenation image data from multi-spectral retinal images, and formation of a retinal metabolic image based on haemoglobin oxygenation. The retinal metabolic image provides a subjective assessment of retinal haemoglobin oxygenation image data captured within the imaging time period. The retinal function image may be synchronised with an R wave of a subject's electrocardiogram, to study retinal metabolism at a predetermined time in a cardiac cycle of the subject. That is, a predetermined time delay may be allowed between detection of the R wave and formation of a scanned image.
The prior art, therefore, provides: oximetry, an objective assessment of retinal haemoglobin oxygenation within a small portion of a retinal blood vessel; an objective assessment of infrared light reflectance change of the retina to light stimulus; and a subjective assessment of retinal haemoglobin oxygenation image data. The prior art does not provide an objective assessment of retinal metabolism based on haemoglobin oxygenation.